Genetic analysis of familial prostate cancer: Identification of a gene predisposing to prostate cancer (PCaP) on chromosome 1q 42.2-43.

Objectives : To conduct genetic linkage analysis in order to localize predisposition genes for hereditary prostate cancer (CaP), as various epidemiological studies have demonstrated a family aggregation in 15 to 25% of cases, and the development of hereditary forms in 5 to 10% of cases of CaP. Material and Methods : A genetic study on 47 French and German families included 122 patients and 72 subjects considered to be healthy after PSA assay. This study was conducted by linkage analysis of 364 microsatellite markers distributed throughout the genome (on average every 10 cM). Results : Parametric and nonparametric linkage analysis identified a locus on chromosome Iq 42.2-43, which could be with a gene predisposing to Cap (called PCaP). The primary site was confirmed by several markers, using 3 different genetic models. The maximum LOD score (probability of linkage between the locus and the disease) on two-point analysis was 2.7 for the D1S2785 marker. Parametric and nonparametric multipoint analysis provided an HLOD score and an NPL score of 2.2 and 3.1, respectively (with P=0.001). Heterogeneity analysis with calculations of LOD scores by multipoint analysis estimated that up to 50% of hereditary Caps were related to this locus, with a heterogeneity probability of 157/1. Analysis of a subgroup of 9/47 families characterized by early onset Cap (before the age of 60 years) confirmed the very high probability of localization of a predisposition gene at locus 1q42.2-43 for these families (multipoint LOD score and NPL score of 3.31 and 3.32, respectively; with P=0.001). Conclusion : The identification of predisposition genes will eventually allow identification within certain families of those subjects who have inherited the genetic abnormality and who therefore present a high risk of CaP. It will then be possible to perform targeted screening of Cap in order to diagnose CaP as early as possible.